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The in-situ formation at −30°C of the electrophilic phosphinidene complex iPr2NPFe(CO)4, resulting from reaction of dichlorophosphine iPr2NPCl2with Na2Fe(CO)4(Collman's reagent), was demonstrated by trapping reactions with various alkynes. The resulting phosphirenes were obtained in good yields. The reactivity of iPr2NPFe(CO)4is less than that of PhPW(CO)5, which is, however, generated at much higher temperatures. The stabilization of iPr2NPFe(CO)4in the reaction medium is discussed.

In response to the need for a nutrient database which includes trans-fatty acid values for the full complement of foods available in the U.S. food supply, a methodology was developed and applied for adding trans-fatty acid values to the University of Minnesota Nutrition Coordinating Center (NCC) Nutrient Database. Values for 16:1, 18:1, 18:2, and total trans-fatty acids were added to the database. Procedures were established and followed to assign values for all core foods in the database (0% missing). The USDA table, Fat and Fatty Acid Content of Selected Foods Containing Trans- Fatty Acidswas the primary source of trans-fatty acid information. Additional data sources included other nutrient databases and articles in the scientific literature containing trans-fatty acid values for U.S. foods, using appropriate methodologies. For foods in the database which could not be matched to reference sources, trans-fatty acid values were imputed using standardized procedures. Values were determined for both current and discontinued food entries so that the database can be used to estimate trans-fatty acid intakes for current dietary studies, as well as those including dietary data collected in the past.

Highly strained methylenephosphiranes are formed in the reaction of the new electrophilic phosphinidene complex [iPr2N−P=Fe(CO)4] with allenes. Remarkably, reaction with diallenes at 0°C also leads to a phosphirane, which rearranges upon warming to room temperature to a bis-isopropylidenephospholene (see scheme).

Dimers both in the crystalline state and in solution: Lithium amides 1aand 2(NLi/N(Me)R = 1/2) are present as dimers (1a)2and 22in the crystalline state and, presumably with the same structures, in toluene and in THF. Lithium amide 3a(NLi/NMe2= 1/1) prevails in THF as the disolvated monomer 3a⋅2 THF. All three amides are broken down into solvent‐separated ions pairs by HMPA.

Hochgespannte Methylenphosphirane entstehen bei der Reaktion des neuartigen, in situ erzeugten elektrophilen Phosphinidenkomplexes [iPr2N−P=Fe(CO)4] mit Allenen. Bemerkenswerterweise führt die Reaktion mit Diallen bei 0°C ebenfalls zu einem Phosphiran, das sich beim Erwärmen auf Raumtemperatur zu einem Bisisopropylidenphosphol umlagert (siehe Schema).

Accurate characterization of the association between carotenoid intake and various chronic diseases requires a current and complete food composition database of individual carotenoid values. The previous database, the 1993 USDA-NCI Carotenoid Database, was updated following a comprehensive review of new carotenoid literature and extensive analysis of carotenoid-containing foods sampled from major metropolitan areas of the U.S. The 1993 procedures were modified to accommodate recent developments in analytical methodology and changes in criteria for numbers of samples. Values for α-carotene, β-carotene, lutein+zeaxanthin, lycopene and β-cryptoxanthin from approximately 200 references were evaluated for the update. In addition to values for these carotenoids, tables include zeaxanthin values for a limited number of foods. The new database was created using previous data, new acceptable literature values, and new analytical data to yield a database of 215 foods. Mean values, standard errors, number of studies, and confidence codes were tabulated for each food. USDA Nutrient Data Bank numbers were assigned to facilitate the use of the carotenoid data with other USDA data. This resulted in the disaggregation of many food item descriptions listed in the 1993 database. An electronic version of the new USDA-NCC Carotenoid Database is available at http:/www.nal.usda.gov/fnic/foodcomp.

Complexes of t-BuLi monomer with 1,4,7-trimethyl-1,4,7-triazacyclononane (TMTAN, 3-CH3) and tris(N,N-dimethyl-2-aminoethyl)amine (4-CH3) were identified by 13C-NMR. Rapid elimination of LiN(CH2CH2NMe2)2takes place from the free CH2CH2NMe2group of t-BuLi·4-CH3. BuLi complexes of hexamethyltriethylenetetramine (5-CH3) and octamethylpentaethylenehexamine (6) behave similarly, as does 4-CH2Li. Complexes of BuLi oligomers are lithiated at free N-CH3. © 1997 Elsevier Science Ltd.

Surgical correction of severe rheumatoid forefoot deformities with resection arthroplasties of the lesser metatarsal phalangeal joints and arthrodesis of the first metatarsal phalangeal joint resulted in a significant long-term improvement with respect to shoe wear, pain, and the ability to stand and walk in 95% of the patients. Ninety percent had a good or excellent functional result. There was minimal recurrence of deformity.Modifications of the procedure with maintenance of the proximal phalangeal bases and K-wire fixation of the metatarsal phalangeal arthroplasty and interphalangeal joints resulted in an improved cosmetic result and simplified postoperative management with an equal functional result and no increase in recurrence of deformity or complications.

When used to assess the nutrient content of diets, recipes, or commercial food products, a nutrient database should provide a complete nutrient profile for each food in the database. Chemical analyses for a wide range of nutrients in the many foods included in a database are not always practical. Therefore, some nutrient values must be estimated. Common methods for estimating nutrient values include (1) using values from a different but similar food, (2) calculating values from different forms of the same food, (3) calculating values from other components in the same food, (4) calculating values from household recipes or commercial product formulations for multicomponent foods, (5) converting values from information on the nutrient label of a commercial food product, (6) calculating values from a product standard, and (7) assuming a zero value. Quality control procedures and nutrient validation programs should be implemented to verify that appropriate data selection, calculation methods, and data entry were used. Estimated nutrient values should be identified in the database. Some referencing systems also indicate the method used to derive each estimated value.

An instrument is described for the measurement of circular and linear polarizations of the luminescence with a time resolution up to 50 ns. The spectrometer, which makes use of a 50-kHz photoelastic modulator and a differential photon-counting technique, is accurate and absolute and is capable of detecting small degrees of polarization. Making use of excitation light pulses which lie randomly in the modulator's duty cycle, the instrument can be readily interfaced with a variety of externally triggered or free running pulsed light sources.

The international significance of this article is summed up by the authors in the concluding remarks: "Perhaps the experiences of school psychology within this changing frontier - Alaska - are not unlike the stories being written in other nations evolving their own educational practices".

The importance of the early childhood years in a child's growth and development cannot be overemphasized. During these years growth is rapid and the foundations for later sensory, motor, cognitive, physical, language and social-emotional development are laid. Some of our most prominent and respected scientists, theoreticians and scholars have emphasized these critical early years (Bloom, 1964; Bronfenbrenner, 1975; Bruner, 1969; Hunt, 1961; White, 1975) and evidence gathered during the last thirty years supports their early work.

N-lithio-N,N',N'',N''-tetramethyldiethylenetriamine (I-Li) is formed from 2,5,8,11-tetramethyl-2,5,8,11-tetraazadodecane (III) or from 2,5,8,11,14,17-hexamethyl-2,5,8,11,14,17-hexaazaoctadecane (IV) with n-BuLi or sec-BuLi, respectively, its isomer N' -lithio-N,N,N'',N'',-tetramethyldiethylene-triamine (II-Li) from tris(2-dimethylaminoethyl)amine (V) with n-BuLi. IV results from treatment of N-lithiomethyl-N,N',N'',N''-tetramethyldiethylenetriamine (PMDTA-Li) with 1,2-dibromoethane.

Two aspects of the heliotropic responses of leaflets of V. unguiculata cv. California Blackeye No. 5 were studied: the environmental conditions responsible for the responses, and the significance of the leaflet orientation responses for adaptation. In the field under drought conditions, leaflets were observed to sun-track (diaheliotropism) in the morning and sun-avoid (paraheliotropism) by becoming more vertical in the afternoon. Overnight irrigation of droughted plants in the field resulted in leaflet movements on the day after irrigation similar to those of the well watered plants. Leaflets of well watered plants were diaheliotropic during the morning and evening, and essentially horizontal during the late morning and afternoon. Controlled-environment studies confirmed field observations of drought effects on leaflet movement and showed that leaflet orientation responses are reversible within 3 h after irrigating droughted plants. Temperature variations similar to those experienced in the field had only small effects on leaflet orientation. Vertical leaflet movement affected canopy architecture and significantly reduced percentage cover at midday. Manually moving the vertical leaflets of droughted plants caused substantial changes in leaflet temperatures, indicating that leaflet movement could substantially reduce heat load, water use, and water deficits in cowpeas.

Although Plato consistently criticized the objectionable use of rhetoric in his day, many have interpreted his Phaedrus as a recognition that rhetoric, in its pure form, is a just and honorable thing. This article attempts to refute this thesis by demonstrating that Plato, in writing Phaedrus, unequivocally affirmed his opposition to rhetoric by constructing an unapproachable ideal rhetoric that, by contrast, put real rhetoric in a permanently unwholesome light.

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No Abstract Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2000/z_s.pdf or from the author.

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Several tetraalkylammonium pentaorganosilicates, derived from 9,9-spirobi(9H,9-silafluorene) were prepared from the corresponding lithium silicates and isolated and characterized as storable high melting solids.

MicroRNAs (miRNAs) are 19–25 nucleotide long RNA molecules derived from precursor genes that inhibit the expression of target genes by binding to their 3′ UTR region. Expression of miRNAs is often tissue specific and miRNA profiling has shown specific miRNA expression patterns in both B-cell development and lymphomagenesis. Hodgkin lymphoma is derived from pre-apoptotic germinal center B-cells, although a general loss of B cell phenotype is noted. Using quantitative RT-PCR and miRNA microarray, we determined the miRNA profile of HL and compared this with the profile of a panel of B-cell non-Hodgkin lymphomas (NHL). The two methods showed a very good correlation for the expression levels of the individual miRNAs. Using a large panel of cell lines, we confirmed differential expression between HL and other B-cell lymphoma derived cell lines for 27 miRNAs. The HL specific miRNAs included miR-155, miR-21 and miR-106b seed family members miR-17-5p, miR-20a, miR-93, miR-106a and miR- 106b. Next, we performed target gene validation of predicted target genes for miR-17-5p, which is highly expressed in HL. Using luciferase reporter assays with stabilized anti-sense miR17-5p oligonucleotides, we showed that GPR137B, RAB12 and RBJ are likely miR-17-5p target genes in two different HL cell lines. Previous publications indicated that miR-106b seed family members negatively regulate the cyclin-dependent kinase inhibitor 1A (p21/CIP1) resulting in cell cycle arrest at G1. Consistent with these findings, we show that the miR-106b family members are highly expressed in L428, whereas p21 is not. However, inhibition of the miR-106b seed family members in L428 does not result in elevated p21 protein expression. Furthermore, there is no cell cycle arrest, growth reduction or increase in cell death and apoptosis after inhibition of the miR-106b seed family members. Thus, we conclude that blocking of the miR-106b seed family members does not necessarily lead to indiction of p21 protein. This suggests an additional regulatory layer of p21 expression in L428 cells.

MiRNAs are small regulatory RNAs which control gene expression at the post-transcriptional level. Tumor cells of Hodgkin lymphoma (HL), the so-called Hodgkin Reed-Sternberg (HRS) cells, originate from defective germinal center B cells. HRS cells are characterized by their loss of B cell phenotype, large multi-nucleated cell size, a disturbed cell cycle and resistance to undergo apoptosis. The aim of our study is to investigate the role of deregulated miRNA expression to the pathogenesis of HL. To identify genes which are regulated by miRNAs in a high throughput manner, an approach called Ribonucleoprotein ImmunoPrecipitation – microarray (RIP-CHIP) was applied. As a first step, the AGO2 protein, which is part of the RISC complex, is immunoprecipitated (IP) with an AGO2 specific antibody. RNA isolation of the IP fraction followed by microarray analysis thus leads to the identification of miRNA targets from the whole transcriptome. With this approach, 1255 genes were found to be commonly regulated by miRNAs in both L1236 and L428 HL cell lines. Genes known to be absent or down regulated in HRS cells, like CDKN1A, CDKN1B, and PRDM1, were included in this gene list. Gene ontology analysis of these candidate miRNA target genes using Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed a significant enrichment in KEGG pathways termed p53 signaling pathway and cell cycle. TargetScan prediction and seed sequence search at the 3′UTRs of these genes both indicated that about half of these genes were targets of the highly abundant miRNAs found in Hodgkin lymphoma cell lines. 10 randomly selected target genes were analyzed using luciferase reporter assays. For all genes, targeting by the predicted miRNA was confirmed using specific antisense Locked Nucleic Acids (LNA) inhibitors. In conclusion, we demonstrated an approach for large scale identification of endogenous miRNA targets without prior manipulation of the cells. HL specific target genes that may contribute to the characteristic phenotype of HRS cells and to the malignant transformation of germinal center B cells were identified.

MiRNAs are a new class of small RNAs, of 19–23 nucleotides that were discovered less than two decades ago. These tiny RNAs can negatively regulate genes at the post-transcriptional level by either triggering translational repression or direct cleavage of mRNAs. It has become evident that miRNAs are involved in hematopoiesis and that the aberrant expression of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to characterize the miRNA profile of naïve, germinal center and memory B cells sorted from tonsils and review expression of selected miRNAs in tonsils and in B cell malignancies by miRNA in situ hybridization (ISH). Quantitative (q)RT-PCR profiling revealed that several miRNAs were elevated in germinal center B cells, including miR-17–5p, miR-106a and miR-181b. miR-150 was one of the most abundant miRNAs in all subsets, but the expression level was more than 10 fold lower in germinal center B cell as compared to the other two subsets. MiRNA ISH on tonsillar tissue sections confirmed findings from the profiling work, and at the same time depicted differences in staining intensities within germinal centers. According to miRNA ISH, expression levels of miR-17-5p, miR-106a, and miR-181b were indeed higher in germinal center B cells as compared to naïve and memory B cells in the mantle zone. Surprisingly, we also observed gradual decrease of miR-17-5p, miR-106a, and miR-181b staining from dark to light zone in the germinal centers. Moreover, miRNA ISH with a probe for miR-150 demonstrated an interesting staining pattern in lymph node tissue sections. Naïve and memory B cells located in the mantle zone showed a higher miR-150 expression as compared to most of the cells in the germinal centers. However, within the germinal centers a minority of cells showed a much stronger cytoplasmic staining in part of the blasts located specifically in the dark zone. This indicated that part of the centroblasts have a high expression level of miR-150. The level of miR-150 was surprisingly low in 22 B cell lymphoma cell lines, irrespective of germinal center or non germinal center B cell origin. This seemingly negative association of miR-150 with proliferation suggests a role in B cell growth/death. We observed an inverse expression pattern of miR-150 and Survivin in the germinal centers by miRNA ISH and immunohistochemistry. Moreover, induction of miR-150 using synthetic mature miR-150 duplex resulted in reduced Survivin expression levels. Our results suggested that aside the experimentally proven target c-Myb, Survivin may also be regulated by miR-150. In conclusion, we have revealed a unique miRNA profile of naïve, germinal center and memory B cells sorted from normal tonsils and the results were confirmed by miRNA ISH. Within the germinal centers a marked difference was observed between the light zone and the dark zone.

Introduction Amplification of chromosome 13q31 is a frequent occurrence in lymphoma and solid tumors. The C13orf25 gene at 13q31.3 is the primary miRNA transcript for seven miRNAs. This specific cluster of miRNAs is sequentially related to the homologous miR-106a-92 cluster on chromosome X and the miR-106b-25 cluster on chromosome 7. The miR17-92 cluster has been shown to be over expressed in various non-Hodgkin Lymphoma (NHL). As a specific group of miRNAs which are derived from the same primary miRNA transcript, each miRNA in the cluster may be expected to show a similar expression level. However expression patterns vary markedly in different cancers. Aim of study To compare the expression pattern of the C13orf25 gene and the miRNAs in normal and malignant B-cells. Methods and Materials 51 cases of Ann Abour stage I and II primary diffuse large B-cell lymphoma (DLBCL) were collected together with 29 cases of B-CLL. All samples were examined for expression of miRNA miR-18a, -19, -20a, 17-3p, -17-5p and -92 and the C13orf 25 gene. Expression levels of the mature miRNAs were determined by qRT-PCR using Taqman miRNA assays. The level of C13orf25 was also determined by qRT-PCR using random primers and a Sybergreen probe. Results were compared by using 2−ΔCt and 2−ΔΔCt. Normal B-cell subpopulations were isolated from fresh tonsils obtained during routine pediatric tonsillectomies. B-cell subsets were stained accordingly and sorted by FACS. Results Comparison of the miRNA pattern (2−ΔCt) revealed that DLBCL have the highest expression level of miR-19b and that B-CLL shows a relative high expression level of miR-92. Normal naïve, germinal center and memory B-cells all show a similar expression pattern with miR-92 having the highest expression level. Remarkably a low expression level of miR-19b is seen in all three B-cell populations in contrast to DLBCL. Comparing the relative expression levels (2−ΔΔCt) of both NHL for each individual miRNA shows that B-CLL has a significantly higher level of expression for miR-19a. In DLBCL miR-17-5p, miR-18a and miR-20a have the highest expression levels. Currently 20 Mantle cell lymphoma are also being analyzed for the C13orf25 miRNAs cluster. Conclusion Our results show that both of the NHL B-cell malignancies and the B-cell subsets have different expression patterns of the individual levels of the 7 miRNAs contained in the same C13orf25 cluster. The relative expression levels of certain miRNAs from the same primary transcript are different in various NHL. Although there are no marked differences in the normal B-cell subsets for the C13orf25 cluster, further profiling revealed various different expression levels of other miRNAs. These findings may point towards a difference in processing efficiency or stability of miRNAs in the C13orf25 cluster leading to differences in pathogenesis specific for each malignancy even in cells of similar origin and differentiation stage.

Introduction Classical Hodgkin lymphoma (cHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) differs not only in the form of histology and reactive background but also in the phenotypes of the tumor cells. Although tumor cells from both HL subtypes are originated from the germinal center (GC) B cell, gene expression studies show that lymphocytic and histiocytic (L&H) cells from NLPHL resembles normal B cells while Hodgkin/Reed-Sternberg cells (H/RS) from cHL demonstrate a loss of B cell phenotype and have significant overlap with primary mediastinal B cell lymphoma (PMBL). Recently, a new class of small RNAs, namely the micro-RNAs (miRNAs), has been identified. It is now known that at the post-transcriptional level, miRNAs negatively regulate gene expression in a sequence specific manner. Unique miRNAs expression patterns have been reported in various tissue types and also during a wide range of physiological states, such as cell proliferation, development, differentiation, apoptosis and hypoxia. As miRNAs play important roles in many cellular processes, it is proposed that there is a link between aberrant miRNA expression and loss of B cell phenotype in cHL.

Introduction: B cell Chronic Lymphocytic Leukemia (B-CLL) is characterized by the accumulation of nonproliferating mature-appearing lymphocytes in the blood, marrow, lymph nodes, and spleen. B-CLL behaves like leukemia and is found mostly in the blood. The expression of ZAP-70 and mutation status of the immunoglobulin heavy-chain gene (IgH) can serve as prognostic markers in B-CLL. ZAP-70 positive cases usually present with unmutated IgH genes and have a bad prognosis, whereas ZAP-70 negative cases mostly present with mutated IgH genes and have good prognosis. Gene expression studies of B-CLL indicated that the profile of IgH mutated and unmutated cases are similar to normal memory B cells. Several studies showed that miRNAs play important roles in pathogenesis of B-CLL and some miRNAs correlate with the prognosis in B-CLL. B-SLL is considered to be the same disease entity as CLL, but this variant is found mostly in bone marrow and the lymphatic system. The most aggressive type of B-SLL is characterized by neoplastic cells that are more responsive to B-cell receptor signaling and are characterized by proliferation centers (PCs), a potentially important site of neoplastic cell stimulation. Until now, only a few reports have been published about the ZAP-70 expression and IgH mutation status and no data are available about the microRNA expression profile. Methods: 33 B-SLL cases were retrieved from the pathology files. ZAP-70 expression was analyzed by using immunohistochemistry. IgH mutation status was determined using PCR followed by direct sequencing. Cases with homology of ≥98% with germline sequences were considered as unmutated and cases with homologies <98% as mutated. Levels of 15 miRNAs were determined by qRT-PCR using U6 as a housekeeping gene in 28 B-SLL cases with good quality RNA. As a control we also analyzed miRNA levels in normal naïve, GC and memory B cell subsets. RNA in-situ hybridization (ISH) was used to localize the most abundantly expressed miRNAs in B-SLL tissues. Results: 16 B-CLL cases were ZAP70+ with the vast majority of tumor cells staining positive and 17 were negative. Of the ZAP70+ cases 10 carried unmutated and 3 mutated IgH genes and 3 cases failed due to bad quality DNA. 14/17 ZAP-70- cases carried mutated IgH genes and 3 cases failed. miR-150, miR-21, miR-16, miR-92 and miR-155 were expressed at high levels in all B-SLL cases independent of the ZAP70 and IgH mutation status. The miRNA expression pattern in B-SLL was very similar to normal memory B cells. RNA-ISH for BIC, the primary transcript of miR-155, demonstrated the most abundant expression in the proliferation centers of B-SLL cases. Conclusion: In B-SLL there is significant correlation between ZAP-70 expression and IgH mutation status similar to B-CLL cases. miRNA expression levels in B-SLL did not correlate with ZAP-70 or IgH status. The overall expression profile is very similar to normal memory B cells. BIC/miR-155 expression is observed specifically in the proliferation center of B-SLL tissues.

The cover picture shows the synthesis of three novel phosphorus-based macrocycles with acetylenic scaffolds from simple and accessible building blocks. The 14-membered macrocycle was obtained as cis and trans isomers from cyclization of diisopropylphosphoramidic dibromide and 1,2-bis(ethynyl)benzene. The four- and six-edged macrocycles in which the iPr2NP(O) units are connected through 1,3-butadiyne rods were obtained after multiple acetylene coupling reactions under oxidative Hay conditions starting from the diethynylphosphinic amide building block. Further details are discussed in the article by K. Lammertsma et al. on p 2405 ff.